The goal of this research application is to evaluate residual central nervous system effects of previous MDMA (3, 4-methylenedioxymethamphetamine or 'Ecstasy') use. Considerable evidence from animal and human studies suggests that MDMA can substantially affect serotonergic reuptake, such that its repletion mechanisms may be permanently altered. The present application proposes to employ sophisticated electroencephalographic (EEG), sensory auditory brainstem responses (ABRs), and cognitive event-related brain potential (ERP) paradigms to assess the central nervous system (CNS) functional effects of MDMA use. This goal will be implemented in two phases: STUDY 1addresses the issue of whether specific CNS deficits result from MDMA use by assaying young adult recreational MDMA users, polydrug users with no MDMA exposure, and control subjects with no drug exposure. Based on previous data reviewed herein, it is likely that appreciable group differences will be found and the CNS effects of MDMA can be characterized. STUDY 2will extend this approach by assessing individuals who differ in their lifetime level of MDMA exposure by comparing occasional (1-5 occasions of MDMA use) and heavy (20+ occasions of MDMA use) users. Survey data of local university populations indicate that such individuals are readily available. In addition, both studies will use sufficiently large samples of female and male subjects so that possible gender differences for MDMA effects can be ascertained. The proposed neuroelectric measures will delineate the general cortical areas (EEG), brainstem (ABRs), and cognitive attention and memory processes (ERPs) affected by MDMA use. This approach will optimize CNS neuroelectric differences between MDMA and other drugs in young adult MDMA users. In particular, the proposed ERP paradigms are designed to provide a comprehensive assessment of MDMA effects on cognitive capability by assaying a variety of factors. These results will provide fundamental data on how MDMA use may alter CNS function.